Composition of hypochlorous acid and its applications

ABSTRACT

Composition of Hypochlorous acid characterized because it has the following chemical composition
         Hypochlorous acid 6.5-7.3%   Hydrochloric acid 27.6-28.5%   Sodium chloride 13.6-14.2%   Sodium hypochlorite 34.8-35.4%   Chlorine in solution 7-6.5%   Dissolved oxygen 10.5-8.1%       

     The composition of hypochlorous acid has medical application in humans and in veterinary practice, both prophylactic and therapeutic. It can also be applied in antisepsis and sterilization of foods and in the treatment of water and water supply systems. In flower growing is can be used for the disinfection of crops and the elimination of fusarium and sigatoka negra.

TECHNICAL

This Application for a Patent of Invention refers to a Composition ofHypochlorous Acid and its different applications especially in the fieldof medicine, such as prophylactic and therapeutic treatment for controlof infections.

BACKGROUND

After 1915, and as a result of the Great War, more than 200 bacterialaction compounds were studied, among them hypochlorous acid. It wasinitially detected as an oxidating agent generated by neutrophiles. Itwas obtained from seawater.

There are references of studies by Dakin in 1917 with sodiumhypochlorite diluted to 0.50% as an irrigation liquid for the cleaningand disinfection of contaminated wounds.

Later, in 1958, Agnes investigated hypochlorous acid as an immunologicalsubstance and defense mechanisms for granulocytes.

In 1989 Stephan J,. Weiss in the New England Journal of medicineconducted bacterial sensitivity studies on E. Coli and toxicity ontissue in guinea-pigs.

There are currently several patents of invention related to theproduction of hypochlorous acid, as mentioned below:

U.S. Pat. No. 4,190,638 “Production of hypochlorous acid”, owned by PPGIndustries Inc., of Feb. 26, 1980 in which aqueous acid is produced byprecipitating the acid through carbonation in a electrolytic cell wherethe cathode is liquid which is placed in contact with a bed fluidizedwith a mixture of gaseous chlorine and water vapor where the gas whichis formed from the hypochlorous bed is absorbed by the water.

U.S. Pat. No. 4,908,215 “Hypochlorite compositions containingthiosulphate and their use” of Mar. 13, 1990, which discloses a processfor disinfection, sterilization, bleaching and cleaning of a liquid or asurface comprised of: (a) producing an aqueous solution of hypochlorite,thiosulphate of earthy alkaline metal and a prebuffer in which thehypochlorite has an initial concentration of about 5 to 5000 ppm ofchlorine and a molar ratio of thiosulphate to hypochlorite between0.25:1 and 0.75: 1; (b) adjusting the initial pH of the solution between9,.0 and 11.0 in contact with the surface or the liquid with thesolution until the hypochlorite is consumed and the pH of the prebuffersolution decreases while the hypochlorite is consumed by thethiosulphate at the same time as the hypochlorite begins to depend onthe initial pH of the solution.

U.S. Pat. No. 5,027,627 “Production of Hypochlorous Acid” published onAug. 6, 1991, where hypochlorous acid is obtained by reaction of anaqueous solution of an alkaline metal hydroxide, forming drops with thegaseous chlorine to produce hypochlorous acid in vapor and particles ofsolid alkaline metal; a process where the molar ratio of the gaseouschlorine to the alkaline metal hydroxide is kept at least 22:1, Theprocess includes the formation of impure chlorate in chlorinatedalkaline metal particles. The hypochlorous acid produced contains 35-60%of weight dissolved in concentrated chlorine of at least about 2% byweight and is substantially free of ions of the alkaline metal andchlorine.

U.S. Pat. No. 5,322,677 “Process for the production of a concentratedsolution of hypochlorous acid”, owned by Oil Corporation, published onJun. 21, 1994, a process which consists of the obtaining of an aqueoushypochloric acid solution having an HOCl concentration of 50-60% byweight, which comprises making a aqueous solution of an alkaline metalhydroxide with 50% by weight with excess of chlorine gas react, makingthem react at 80-120 deg. C. to produce a mixture of monoxide, chlorine,hypochlorous acid vapor and water vapor, solid particles of chloratealkaline metal of at least 10%.

WO 9514636 “Manufacture of Hypochlorous Acid” owned by Joseph Repman,The Dow Chemical Company Trent and David, L., published Jun. 1, 1995, aprocess which consists of placed in contact the drops of a aqueoussolution of hypochlorite metal having an intermediate volume, a diameterof 500 mm with chlorine gas to produce hypochlorous acid, vaporizationof 20% m of hypochlorous acid produced in the preceding stage,containing chlorine, water vapor, hypochlorous acid and dichloridemonoxide within an aqueous phase of acid.

ADVANTAGES OF THE INVENTION

The patent of invention Composition of Hypochlorous Acid and its variousapplications has the following advantage over others in the state of theart:

-   -   The composition of hypochlorous acid is not toxic and does not        attack the skin    -   The composition is fully biodegradable    -   Disinfection occurs in seconds given the broader disinfection        spectrum    -   As a deodorant it destroys organic particles since it attacks        mercaptane, methane and hydrosulphuric gases.    -   It has bacteriostatic powers for up to 24 hours    -   The process if obtaining the composition is economical, due to        its ample dilution.

DISCLOSURE OF THE INVENTION

The concern to find substances which do not cause reactions in theorganism and are highly effective in combating microorganisms resistantto antimicrobial agents and drugs has led to the study of hypochlorousacid, a substance which as the characteristics of minimizing morbidityand mortality produced by bacterial infections in comparison with normalsaline solutions, a substance mostly used for washing the abdominalcavity and tissues.

Hypochlorous acid (HOCl) is a bactericide oxidant known particularly asan aqueous solution which attacks microorganisms in the place where theyare produced, dependent on 02. In particular, it reacts modifyingvarious high-density proteins (aminoacids, lipids) which are first foundin the plasma or the proteins of the plasmatic membrane, inhibitingsynthesis.

Hypochlorous acid is an unstable compound, highly reactive, thestrongest of the hypo halogenated acids and one of the most powerfuloxidating agents among chlorate oxacids. It is a weak acid with adissociation constant of 2.9+10−8 at 25 deg. C., it is stable in colddiluted and pure solutions. The acid reacts with peroxide and gives offoxygen.

Half of the protein is highly toxic to cells; it deactivates or inhibitsseveral systems of the endoplasmatic reticule carrier (transport ofglucose, several transporters of amino acids, Na+/K-ATPase.) andgenerally causes harm to small molecules, making the cell inflate andsubsequently causing cell death.

It can cause the death of highly resistant bacterial spores, all typesof virus, macrobacterium with serous capsule (TB), all other vegetativebacteria and fungi in a concentration of 0.2% compared to otherhigh-level microbicide substances such as alkaline glutaraldehyde at 2%or hydrogen peroxide. HOCl can damage isolated DNA, cell death precedesoxidation of DNA in whole cells, and the sum of mieloperoxide inhibitsinduced oxygen peroxide H2O2 and breaks down the DNA structure.

Chlorine concentrations of 0.25 which are effective bactericides formany microorganisms except microbacteria, which are 500 times moreresistant. Organic material in great part reduces antimicrobial activityof chlorine.

It is a bactericide agent which attacks microorganisms at the placewhere they proliferate, prepared in the immune system by nuclearpolymorph neutrophiles which migrate and adhere to the endothelial cellsto act as a mediator in inflammation, increasing the permeability of thevascular endothelium for cellular participation and to kill antigens.This substance is produced by hydrogen peroxide (H2O2), a chlorine ion,in reaction with the enzyme mieloperoxidase.

Mieloperoxidase converts H2O2 into a reasonable microbicidal agent andHOCl into an excellent one; at the same time it diverts the genotoxicH2O2 into HOCl which is highly toxic for the tissue in a free proteinsystem, but which is considerably less toxic in vivo.

The composition of hypochlorous acid object of this patent of inventionis a solution of hypochlorous acid with a content of 17 g/l of availablechlorine. The physical properties are as follows:

Formula HOCl Appearance Crystalline Odor Characteristic of chlorineChlorine (g/l) Max 16-18 pH 5-6 Density (g/ml) 0.9-1-05 Solids None ORP1250-1450 mv

The chemical composition is:

-   -   Hypochlorous acid 6.5-7.3%    -   Hydrochloric acid 27.6-28.5%    -   Sodium chloride 13.6-14.2%    -   Sodium hypochlorite 34.8-35.4%    -   Chlorine in solution 7-6.5%    -   Dissolved oxygen 10.5-8.1%

The stability of the solution depends on:

-   -   Chlorine concentration    -   pH of the solution    -   Temperature of the solution    -   Exposure to light

The spectrum shown by the composition of hypochlorous acid is asfollows:

-   -   HIV    -   Staphylococcus aureus    -   Hemolitic Streptococcus    -   Coagulaze staphylococcus (−Y+)    -   Enterobacter aerogenes    -   Salmonella    -   Clostridium    -   Aspergillus flavus    -   Bacillus SPP    -   Pseudomonas    -   Pulmonary Klebsiella    -   Escherichia Coli

The tissular action of the composition of hypochlorous acid isparticularly notable in three areas:

-   -   1. Antiseptic: direct germicidal action, like any other        chlorate. This action is a known and classic one    -   2. Granulant: through a local increase in the repair cells,        since studies have shown a local increase in fibroblasts.    -   3. Local increase in immunological activity; when the action of        the granulosites is triggered locally. It is well-known that the        two principal mechanisms of defense of the neutrophiles and        other defensive cells are the production of oxidants which fire        off at the aggressor germ: peroxides and hypochlorous acid.

APPLICATIONS OF THE COMPOSITION

The composition of hypochlorous acid, object of this application for apatent of invention, in the field of medicine, has its principalapplication in:

1.—Medical

1.2 Therapy

1.1.1 For antisepsis and granulation of infected tissues, abscesses,cellulitis etc. With excellent results for curing infectious events ofsubcutaneous cell tissue, whether with open or closed tissue or with nowound.

1.2.1 Ulcers on the lower limbs. The surface should remain in contactwith the product

1.3.1 Exposed surfaces and open cuts, in infected cavities such asperitonitis and empyema

1.4.1 In infectious sinusitis and rhinitis

1.5.1 Intra-articular for treatment of septic arthritis. Use inorthopedic-osseous infectious events

1.2 Prophlaxis

a) Washing of clean and contaminated surgical wounds

b) Local cleaning of the peritoneal cavity for appendicitis andcolecystitis, in rdumentary form

c) Antisepsis of surfaces and elements

2. Non Medical

1. Antisepsis and sterilization of food

2. Treatment of water and water supply systems.

3. Disinfection of crops.

4. Elimination of fusarium and sigatoka negra.

EXAMPLES OF APPLICATION

Abdominal Surgery

300 trials of the composition of hypochlorous acid at 5000 ppm have beeneffected in the systematic washing of surgical wounds and of theperitoneal cavity, local or generalized.

Wounds were evaluated, along with evolution by Swan's table ofclassification of infection of surgical wounds.

The results were:

-   -   An average of 4 washes was required with only the hypochlorous        acid composition, a laparotomy closing was achieved with an        average of 5-15 washes

Cultures were negativized with the third wash and 4 E Coli and 2Pseudonomes were obtained. Neither re-laparotomy nor abscesses werenecessary

The index of infection of the surgical wound fell to 1.0% (10%-25% indifferent series) for appendicectomy in different studies.

The results are detailed in the chart below:

Without Localized Generalized peritonitis peritonitis peritonitisLaparostomy Edematose 60 appendicitis Suppurative 92 58 appendicitisPerforated 38 22 4 appendicitis Perforated colon 3 diverticulus Multiplewound 10 10 laparotomy Septic uterine 1 perforationVascular Pathology of Lower Limits

Over 2090 cases were handled. The hypochlorous acid composition was usedat 5% un ulcerous lesions of arterial/venous origin, surgical wounds,prophylactic and therapeutic amputations, it being recommended that theaffected zone be kept damp with the liquid, for local use only.

Specific studies were performed on patients with more prolonged use forkidney, liver and modular functions, without finding any alteration inthese organs.

In addition there were toxicology studies, and no levels of hypochlorousacid were found in urine or blood.

Biopsies were evaluated by pathology, showing the effected describedpreviously by other authors, of a local increase in fibroblasts incomparison to patients not using the composition.

The results were:

-   -   As with the abdominal pathology, it is difficult to standardize        on the basis of size, depth, origin and state of the        ulcerations. Consideration was given to:    -   Excellent/very good: 88%, where there was full cure of the        ulcers including refractory lesions from all prior treatment,        infected wounds, traumatic necrosis and ischaemias.    -   Fair: 12%, given by the appearance of granulation tissue and        reduction of the ulcerated area, but without full closure or        cure.

There were reactions considered adverse by erythema of the skin ofbronchial spasm in 1.5% but these ceased when use was suspended in thefirst case.

Cultures and tests of inhibition for staphylococcus aureus, E. Coli andpseudomona were conducted and there was full inhibition in the growth ofall three bacteria when adding hypochlorous acid to the culture agar andin the Petri box, inhibition haloes.

1. A composition of hypochlorous acid having the following chemicalcomposition: hypochlorous acid 6.5-7.3%, hydrochloric acid 27.6-28.5%,sodium chloride 136-14.2%, sodium hypochlorite 34.8-35.4% chlorine insolution 6.5-7%, dissolved oxygen 8.1-10.5%.
 2. The composition ofhypochlorous acid of claim 1 having the following physical properties:pH 5-6, Density (g/ml) 0.9-1.05. Solids Nones, ORP 1250-1450 mV.
 3. Thecomposition of hypochlorous acid of claim 1 where the amount of chlorinevaries from 16 g/l to 18 g/l.
 4. The composition of hypochlorous acid ofclaim 1 where said composition has therapeutic medical application inhuman beings: a) for antisepsis and granulation of infected tissues,abscesses, and cellulitis; b) ulcers on the lower limbs; c) exposedsurfaces and open cuts infected cavities such as peritonitis andempyema; d) in infectious sinusitis and rhinitis; and e) intra-articularfor treatment of septic arthritis.
 5. The composition of hypochlorousacid of claim 1 where said composition has medical application inhumans: a) washing of clean and contaminated surgical wounds; b) localcleaning of the peritoneal cavity for appenficitis and cholecystitis, inrudimentary form; and c) antisepsis of surfaces and elements.
 6. Thecomposition of hypochlorous acid of claim 1, where said composition hasapplications in: a) antisepsis and sterilization of food; and b)treatment of water and water supply systems.
 7. The composition ofhypochlorous acid of claim 1 where said composition has uses inveterinary practice for: a) washing of clean and contaminated surgicalwounds; and b) antisepsis of surfaces and elements.
 8. The compositionof hypochlorous acid in claim 1 where said composition has veterinaryapplication in therapy: a) for antisepsis and granulation of infectedtissues, abscesses; and b) ulcerations of all types.
 9. The compositionof hypochlorous acid in claim 1 where said composition has applicationsin flower-growing: a) to disinfect crops; and b) to eliminate fusariumand sigatoka negra.